Age-Related Changes of Peak Width Skeletonized Mean Diffusivity (PSMD) Across the Adult Lifespan: A Multi-Cohort Study.

Grégory Beaudet,Joanna M Wardlaw,Stéphanie Debette,Marco Duering,A Veronica Witte,Perminder S Sachdev,Ian J Deary,Svenja Caspers,Lukas Pirpamer,Jan Schreiber,Arno Villringer,Yash Patel,Laurent Petit,Reinhold Schmidt,Ami Tsuchida,Christophe Tzourio,Nicola J Armstrong,Bernard Mazoyer,Mark E Bastin,Henry Brodaty,Tomáš Paus ,Wen Wang ,Nicole A Kochan ,Susana Muñoz Maniega ,Julian N Trollor ,Zdenka Pausová

doi:10.3389/fpsyt.2020.00342

Abstract

Parameters of water diffusion in white matter derived from diffusion-weighted imaging (DWI), such as fractional anisotropy (FA), mean, axial, and radial diffusivity (MD, AD, and RD), and more recently, peak width of skeletonized mean diffusivity (PSMD), have been proposed as potential markers of normal and pathological brain ageing. However, their relative evolution over the entire adult lifespan in healthy individuals remains partly unknown during early and late adulthood, and particularly for the PSMD index. Here, we gathered and analyzed cross-sectional diffusion tensor imaging (DTI) data from 10 population-based cohort studies in order to establish the time course of white matter water diffusion phenotypes from post-adolescence to late adulthood. DTI data were obtained from a total of 20,005 individuals aged 18.1 to 92.6 years and analyzed with the same pipeline for computing skeletonized DTI metrics from DTI maps. For each individual, MD, AD, RD, and FA mean values were computed over their FA volume skeleton, PSMD being calculated as the 90% peak width of the MD values distribution across the FA skeleton. Mean values of each DTI metric were found to strongly vary across cohorts, most likely due to major differences in DWI acquisition protocols as well as pre-processing and DTI model fitting. However, age effects on each DTI metric were found to be highly consistent across cohorts. RD, MD, and AD variations with age exhibited the same U-shape pattern, first slowly decreasing during post-adolescence until the age of 30, 40, and 50 years, respectively, then progressively increasing until late life. FA showed a reverse profile, initially increasing then continuously decreasing, slowly until the 70s, then sharply declining thereafter. By contrast, PSMD constantly increased, first slowly until the 60s, then more sharply. These results demonstrate that, in the general population, age affects PSMD in a manner different from that of other DTI metrics. The constant increase in PSMD throughout the entire adult life, including during post-adolescence, indicates that PSMD could be an early marker of the ageing process.

Highlights

We will focus on the original findings regarding peak width of skeletonized mean diffusivity (PSMD) distribution and evolution over the adult life
In order to study the effects of age over the entire adult lifespan, we gathered diffusion tensor imaging (DTI) data from 20,005 individuals scanned at 10 different sites with the major objective of maximizing statistical power
We focused on the mean DTI metrics over a white matter skeleton, rather than over the entire white-matter compartment, since our primary metric of interest was PSMD, which is defined over the FMRIB Software Library (FSL)-TBSS white matter skeleton derived from fractional anisotropy (FA) data

Summary

Introduction

Parameters of water diffusion in white matter derived from diffusion-weighted imaging (DWI), such as fractional anisotropy (FA), mean, axial, and radial diffusivity (MD, AD, and RD) are well-established markers of normal brain maturation [1,2,3,4,5] and ageing [6,7,8,9,10,11,12] and have been proposed as potential tools for the investigation of various brain disorders [13,14,15,16,17,18,19].More recently, peak width of skeletonized mean diffusivity (PSMD) [20], a new phenotype of white matter microstructure that can be derived from DWI, has been proposed as an imaging biomarker of small vessel disease (SVD) [20, 21] and a correlate of cognitive impairment, processing speed [20,21,22]. Parameters of water diffusion in white matter derived from diffusion-weighted imaging (DWI), such as fractional anisotropy (FA), mean, axial, and radial diffusivity (MD, AD, and RD) are well-established markers of normal brain maturation [1,2,3,4,5] and ageing [6,7,8,9,10,11,12] and have been proposed as potential tools for the investigation of various brain disorders [13,14,15,16,17,18,19]. We gathered and analyzed cross-sectional DTI data from 10 population-based cohort studies to establish the time course, from post-adolescence to late adulthood, of the PSMD distribution and compare it with that of more commonly used white matter water diffusion phenotypes in white matter

Objectives

Methods

Conclusion